Implantation of medical devices, such as pacemakers, neurostimulators, implanted drug pumps, leads, catheters, etc. has been associated with adverse consequences, such as formation of scar tissue surrounding the implant and infection due to bacteria introduced during implantation. Attempts to prevent or control such adverse reactions have included administration of drugs, completely separate from the intended primary therapy of the implanted medical device. In some cases, systemically administered drugs, e.g. orally, intravenously, or intramuscularly administered drugs, have proven effective in treating complications due to medical device implantation. In other cases, systemic delivery has been ineffective due to, e.g., pharmacokinetic or pharmacodynamic characteristics of the drug, the location of the implanted device, or side effects of the drug. To increase effectiveness in these situations, some implanted devices have been modified to elute the drug into the surrounding tissues.
One common way of providing local drug elution is to dispose a polymer layer on the implantable medical device and embed the drug into the polymer during manufacturing. When hydrated after implant, the drug diffuses out of the polymer into surrounding tissue. Various methods of impregnating polymers with drugs have been used, including mixing the drug into the melted polymer prior to processing (e.g. molding or extrusion), and diffusing the drug into a finished polymer component using chemicals to swell the polymer for rapid loading. In some cases, the implantable medical device (IMD) is made from a polymer that is compatible with the drug, and the drug can be loaded directly into the device. However, incorporation of a therapeutic agent into or onto polymeric material may compromise the structural integrity of the material.
Structural integrity of catheters and leads, especially those intended to be chronically or permanently implanted, are important. Such catheters and leads, which are typically made using standard polymeric tubing, such as silicone or polyurethane, are tunneled subcutaneously from a pocket into which an active device, such as a drug pump or neurostimulator, is implanted to the therapy delivery site. For neurological systems, the therapy delivery site is typically the spinal intrathecal space, the spinal epidural space, the ventricles of the brain, or brain parenchyma. For cardiac systems, the therapy delivery site is the heart. Because, the catheters and leads are implanted long term and may be tunneled through a subcutaneous path, it may not be desirable to compromise the structural integrity of such devices.
In addition, the active agent disposed on or in the structural body of a catheter or lead can diffuse inward to the catheter drug path or the lead conductors as readily as it diffuses outward to the subcutaneous tissue. Diffusion of the elutable agent into the drug flow path of a catheter may result in undesired interaction of the drug delivered by the catheter and the elutable agent or may cause the elutable agent to be delivered to an area of the body on which its effects may be undersiable. For example, the elutable agent is intended to be delivered to subcutaneous tissue, and may have deleterious effects at the site of therapy delivery, e.g. the central nervous system (CNS). For stimulation leads, the active agent could cause corrosion of the metallic conductors or electrodes. For both types of devices, adding the active agent results in an extra manufacturing process that complicates manufacturing. In addition, the shelf life of a catheter or lead having an associated therapeutic agent may be considerably less than the shelf life of a catheter or lead without an associated therapeutic agent.